Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Cardiovascular 2018 > Antiplatelet, anticoagulant and thrombolytic drugs > Flashcards

Antiplatelet, anticoagulant and thrombolytic drugs Flashcards

1
Q

What is haemostasis?

A

-arrest of blood loss from a damaged vessel- at the site of injury

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Describe the 3 phases of haemostasis?

A
  1. vascular wall damage exposing collagen and tissue factor (TF and thromboplastin)
  2. primary haemostasis
    >local vasoconstriction
    >platelet adhesion, activation and aggregation (by fibrinogen)
  3. activation of blood clotting (coagulation and the formation of a stable clot (by enmeshing platelets)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the outcome of vessel damage in haemostasis?

A

exposes collagen to which platelets bind and become activates

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the role of active platelets in primary haemostasis?

A

> extend pseudopodia (primary protrusion of the surface of an amoeboid cell for movement and feeding)
synthesise and release thromboxane A2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What does thromboxane A2 bind to?

A

> platelet GPCR TXA2 receptors
- causing mediator release [5-hydrocytryptamine (5-HT)] aka serotonin and adenosine phosphate

> vascular smooth muscle cell TXA2 receptors causing vasoconstriction that is augmented by mediator 5-HT binding to smooth muscle GPCR 5-HT receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What does thromboxane A2 cause when it binds to platelet GPCR TXA2 receptors?

A
  • causing mediator release [5-hydrocytryptamine (5-HT)] aka serotonin and adenosine phosphate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What does thromboxane A2 cause when it binds to vascular smooth muscle cell TXA2 receptors?

A

causing vasoconstriction that is augmented by mediator 5-HT binding to smooth muscle GPCR 5-HT receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What does ADP released from platelet receptors bind to?

A

GPCR purine receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What does ADP binding to GPCR purine receptors cause?

A

> act locally to activate further platelets

> aggregate platelets into a soft plug at the site of injury (via increased expression of platelet glycoprotein receptors that bind fibrinogen). TXA2 receptors act similarly

> expose acidic phospholipids on the platelet surgace that initiate coagulation of blood and solid clot formation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the events occurring at the platelet membrane in late in the coagulation cascade?

A
  1. complex, amplifying, cascase in which proenzymes are converted to active enzymes is the production of the protease thrombin (factor IIa) that cleaves fibrinogen to fibrin to form a solid clot
  2. inactive factor X is converted by tenase to the active factor Xa
  3. inactive factor II (prothrombin is converted by prothrombinase to the active factor IIa
  4. fibrinogen is converted by thrombin to fibrin yielding a solid clot
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Describe an arterial thrombus?

A

> white thrombus: mainly platelets in a fibrin mesh

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Where do arterial emboli typically lodge?

A

> forms an embolus if it detatched from its site of origin (e.g. left heart, carotid artery) often lodges in an artery in the brain or other organ

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How are arterial emboli treated?

A

> primarily treated with antiplatelet drugs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Describe a venous thrombus?

A

> red thrombus: white head, jelly like red tail, fibrin rich

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Where do venous emboli typically lodge?

A

> if detatched forms an embolus that usually lodges in the lung

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How are venous emboli treated?

A

> primarily treated with anticoagulants

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Describe the role of vitamin K in clotting?

A
  1. clotting factors II (prothrombin), VII, IX and X are glycoprotein precursors of the active factors IIa (thrombin), VIIa, IXa, and Xa that act as serine proteases
  2. precursors are post-translationally modified (i.e. g-carboxylation of glutamate residues) to produce the active factors
  3. the carboxylase enzyme that mediates g-carboxylation requires vitamin K [Koagulation in German - from diet (K1) and intestinal flora (K2)] in its reduced form as an essential cofactor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

When are anticoagulants used?

A

prevention and treatment of venous thrombosis and embolism

  • deep vein thrombosis (DVT)
  • prevention of post-operative thrombosis
  • patients with artificial heart valves
  • AF
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is the risk with all anticoagulants?

A

Haemorrhage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the significance of vitamin K and warfarin?

A

warfarin is structurally related to vitamin K : competes for binding to hepatic vitamin K reductase preventing production of the active hydroquinone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What factors does warfarin inactivate?

A

II, VII, IX and X

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How is warfarin administered?

A

Orally

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the onset of action of warfarin?

A

slow onset of action (2-3 days) whilst inactive factors replace active g-carboxylated factors that are slowly cleared from the plasma.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What anticoagulant should be used for quick effect?

A

Heparin may be added for rapid anticoagulant effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What is the half life of warfarin?

A

long (and variable) half-life (usually about 40 hr)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What are the warnings associated with warfarin?

A

balance between anticoagulation and haemorrhage

use complicated by delay to maximal effect and several medical and environmental influences

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

How is warfarin monitored?

A

monitored on regular basis as INR ratio

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

How can warfarin overdose be treated?

A

be treated with administration of vitamin K1 as phytomenadione or concentrate of plasma clotting factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What potentiates warfarin action?

A

-liver disease
-high metabolic rate: increased clearance of clotting factors
-drug interactions
>agents that inhibit hepatic metabolism of warfarin by CYP2C9 (consult BNF)
> drugs that inhibit platelet function (e.g. aspirin, other NSAIDs)
>drugs that inhibit reduction, or decrease availability, of vitamin K

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What factors lessen warfarin action?

A

> physiological state - pregnancy (increased clotting factor synthesis) - hypothyroidism (decreased degradation of clotting factors)

> vitamin K consumption

> drug interactions
-agents that increase hepatic metabolism of warfarin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What is antithrombin III?

A

Important inhibitor of coagulation which neutralises all serine protease factors in the coagulation cascade by binding to their active site in a 1 to 1 ratio.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

How does heparin work?

A

Binds to antithrombin III, increasing its affinity for serine protease clotting factors (Xa and IIa) to increase their rate of their inactivation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What is heparin?

A

Heparin is a naturally occurring sulphated glycosaminoglycan of variable molecular size extracted from offal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Name some LMWH?

A

Enoxaparin

Dalteparin

35
Q

How do LMWH work?

A

Inhibit factor Xa but not thrombin IIa

36
Q

How is heparin administered?

A

Administered IV (immediate onset of action) or SC onset delayed by one hour

37
Q

How are LMWH administered

A

SC

38
Q

What is required for heparin dosage (but not LMWH dosage)?

A

in vitro clotting test

39
Q

What is the difference between heparin and HMWH elimination?

A

heparin is zero order and HMWH is first order

40
Q

How is LMWH eliminated?

A

LMWH is eliminated by renal excretion

41
Q

Why is heparin preferred in renal failure?

A

It is not eliminated by renal exxcretion

42
Q

What are the adverse effects of heparin and LMWH?

A

> haemorrhage - discontinue drug, if necessary administer protamine sulfate IV (inactivates heparin)
osteoporosis (long term treatment)
hypoaldosteronism
hypersensitivity reactions

43
Q

What are orally active inhibitors?

A

Newer orally active agents that act as direct inhibitors of thrombin or factor Xa

44
Q

What orally active inhibitors inhibit thrombin?

A

Dabigatran

Etexilate

45
Q

What orally active inhibitors inhibit factor Xa?

A

Rivaroxiban

46
Q

What are the advantages of orally active inhibitors?

A

> convenience of administration
predictable degree of anticoagulation, but no specific agent is available to reduce haemorrhage in overdose which is a major disadvantage

47
Q

When are orally active inhibitors routinely used?

A

prevent venous thrombosis in patients undergoing hip and knee replacement

48
Q

How does clopidogrel work?

A

Blocks the P2Y12 receptor by a disulphide bond irreversibly

49
Q

How does tirofiban work?

A

Blocks the GPIIb/IIIa receptor

50
Q

How does aspirin work?

A

Blocks cyclo-oxgenaase-1 irreversibly in platelets, preventing TXA2 synthesis, but also COX in endothelial cells inhibiting production of prostaglandin I2

51
Q

How does Ifetroben work?

A

Thromboxane synthase

52
Q

When are anti-platelet drugs used?

A

In the treatment of arterial thrombosis

53
Q

How is the balance of aspirin shifted in favour of an anti thrombotic effect?

A

because endothelial cells can synthesise new COX enzyme wherease enucleate platelets cannot. TXA2 synthesis does not recover until affected platelets are replaced (7-10 days)

54
Q

What is aspirin used mainly for?

A

Mainly for thromboprophylaxis in patients at high cardiovascular risk

55
Q

What are the main adverse effects of aspirin?

A

GI bleeding and ulceration

56
Q

When is clopidogrel used?

A

Used in patients intolerable to aspirin

57
Q

How is clopidogrel administered?

A

Administered orally, when combined with aspirin has a synergistic action

58
Q

How is tirofiban administered and when?

A

given IV in short term treatment to prevent myocardial infarction in high risk patients with unstable angina (with aspirin and heparin)

59
Q

What do streptokinase, alteplase and duteplase activate?

A

Activate plasminogen

60
Q

What are fibrinolytics used for?

A

Reopen occluded arteries in acute MI or stroke, less frequently life threatening venous thrombosis or PE

61
Q

How are fibrinolytics administered?

A

IV within as short a period as possible

62
Q

What is superior to fibrinolytics?

A

PCI

63
Q

What is streptokinase?

A

not an enzyme, protein extracted from cultures of streptococci

64
Q

When is streptokinase action blocked?

A

after 4 days by the generation of antibodies

65
Q

Who should not be given streptokinase?

A

may cause allergic reactions (not be given with patients with recent streptococcal infections)

66
Q

What do alteplase and duteplase do?

A

Recombinant tissue plasminogen activators

67
Q

When are alteplase and duteplase most effective?

A

more effective on fibrin bound plasminogen than plasma plasminogen and show selectivity for clots

68
Q

What is the half life of alteplase and duteplase?

A

Short, hence IV infusion

69
Q

What are the adverse effects of alteplase and duteplase?

A

Haemorrhage that may be controlled by tranexcamic acid which inhibits plasminogen activation

70
Q

What is the 1st step in primary haemostasis?

A

Exposed collagen binds von Willebrand factor (vWF) to which platelet glycoprotein Ib (GPIb) receptors also bind

71
Q

What is the 2nd step in primary haemostasis?

A

Tethered’ platelet subsequently binds directly to collagen via its integrin α2β1 and glycoprotein VI (GPVI) receptors - platelet activation is initiated

72
Q

What is the 3rd step in primary haemostasis?

A

The activated platelet:

a. extends pseudopodia
b. synthesises thromboxane A2 (TXA2) from arachidonic acid mediated by the enzyme cyclo-oxygenase-1 (COX-1)

73
Q

What is the 4th step in primary haemostasis?

A

TXA2 binds to platelet GPCR TXA2 receptors causing: omediator release

a. 5-hydroxytryptamine (5-HT) (aka serotonin) and adenosine diphosphate (ADP) from dense granules
b. vWF and factor V from α-granules ovasoconstriction, both direct and indirect via release of 5-HT

74
Q

What is the 5th step in primary haemostasis?

A

(v) ADP binds to platelet GPCR P2Y12 receptors
a. activating further platelets
b. increasing the expression of platelet glycoprotein (GP) Ilb and IIIa receptors that bind fibrinogen (this aggregates the platelets into a ‘soft plug’)
c. exposing acidic phospholipids on the platelet surface - this facilitates formation of the clot by the process of coagulation

75
Q

What is the pivotal even in coagulation?

A

the production of the protease thrombin (factor IIa) that cleaves fibrinogen to fibrin to form a solid clot

76
Q

What is the first step in the initial phase of coagulation?

A
  1. Cells bearing tissue factor (TF, thromboplastin) in the subendothelial matrix are exposed to factor VIIa from the plasma forming a complex (TF:VIIa)
77
Q

What is the second step in the initial phase of coagulation?

A
  1. TF:VIIa activates factor X (X→Xa) which, in combination with its cofactor Va, converts prothrombin (factor II) to thrombin (factor IIa)
78
Q

What is the first step in the amplification phase of coagulation? (at the platelet)

A
  1. Thrombin (factor IIa) activates further platelets
79
Q

What is the second step in the amplification phase of coagulation? (at the platelet)

A
  1. Thrombin also liberates factor Vlll from vWF (to which it is normally bound) and activates it at the platelet membrane
80
Q

What is the first step in the propagation phase of coagulation?

A
  1. Factor XIa (activated by thrombin), or TF:VIIa, activate factor IX. Factor IX forms a complex with factor Vllla termed tenase at the platelet membrane which powerfully activates factor X (more so than TF:Vlla)
81
Q

What is the second step in the propagation phase of coagulation?

A
  1. Factors Xa and Va as a complex bind to prothombinase at the platelet membrane [converting prothrombin (factor II) to thrombin (factor IIa)]
82
Q

What is the third step in the propagation phase of coagulation?

A
  1. Thrombin (factor IIa) cleaves fibrinogen, forming fragments that spontaneously polymerise to form fibrin
83
Q

What is the fourth step in the propagation phase of coagulation?

A
  1. Factor VIIIa (activated by thrombin) cross-links the polymer to form a fibrin fibre network and a solid clot

Cardiovascular 2018 (39 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions